We studied at necropsy 80 opiate addicts with anatomic evidence of active (59 patients) or healed (11 patients) infective endocarditis (IE) or both (10 patients). Of the 80 patients, the first episode of IE involved a single right-sided cardiac valve in 24 patients (30%); both a right- and a left-sided valve in 13 patients (16%); a single left-sided valve in 33 patients (41%), and both left-sided valves in 10 patients (13%). Of the 320 cardiac valves in the 80 patients, 103 were sites of vegetations, an average of 1.3 of the 4 valves. Of the 80 patients, the tricuspid valve was infected in 35 (44%), mitral in 34 (43%), aortic in 32 (40%). and pulmonic in 2 (3%). Of the 103 infected cardiac valves, the infection caused sufficient damage to cause dysfunction in 70 (68%): in 28 (88%) of 32 infected aortic valves; in 22 (53%) of 35 infected tricuspid valves; in 19 (56%) of the 34 infected mitral valves; and in 1 of the 2 infected pulmonic valves. Of the 80 patients, 57 (71%) had sufficient valvular damage to cause valvular dysfunction. Of the 80 patients, gross examination of the valves at necropsy indicated that the infected valve almost certainly had been anatomically normal in 65 patients (81%) and abnormal in 25 patients (19%) before the onset of IE. Of the 65 patients with previously anatomically normal valves, 86 (33%) of their 260 cardiac valves were sites of infection (average 1.3 valves per patient); of the 15 patients with infection superimposed on a previously abnormal valve, the infection in each involved previously abnormal valves (21 in the 15 patients) or 17 (28%) of their 60 cardiac valves were sites of infection (average 1.1 valve per patient). Of the 15 patients with abnormal cardiac valves before the infection, 7 had congenitally bicuspid aortic valves and 8 had diffuse fibrous thickening of the mitral valve typical of rheumatic heart disease with (6 patients) or without (2 patients) diffuse fibrous thickening of 3-cuspid aortic valves.